Differences in renal hemodynamics and renin secretion between patients with unifocal and multifocal fibromuscular dysplasia

Objective: Fibromuscular dysplasia (FMD) can be classified in a multifocal and a unifocal subtype. As unifocal FMD generally leads to more severe hypertension at younger age, we hypothesized that renal hemodynamics are more disturbed in unifocal renal artery FMD as compared with multifocal FMD, leading to increased renin secretion. Methods: We measured renal blood flow ((133)Xenon washout method), renin secretion, and glomerular filtration rate per kidney in 101 patients with FMD (26 unifocal and 75 multifocal), all off medication and prior to balloon angioplasty. Results: We found that renal blood flow and glomerular filtration were substantially lower in kidneys with unifocal FMD as compared with multifocal FMD. In the affected kidney from patients with unilateral FMD for example, mean renal blood flow was 173 +/- 77 in unifocal vs. 244 +/- 79 ml/100 g kidney/min in multifocal FMD (P=0.013). Moreover, lateralization in renin secretion was only observed in a subset of patients with unifocal FMD, but not in any of the patients with multifocal FMD. Conclusion: These findings suggest that the impact of unifocal FMD lesions on the kidney is more severe, resulting in a classical pattern of renovascular hypertension. In multifocal FMD, however, renal blood flow is more preserved, local renin secretion is not increased, and the association between renin levels and blood pressure is inverse. These differences may explain the often more severe clinical presentation and higher success rate of revascularization in unifocal FMD, but also suggest that the pathophysiological mechanisms leading to hypertension may differ between these two disease entities

Data2Game: Towards an Integrated Demonstrator

The Data2Game project investigates how the efficacy of computerized training games can be enhanced by tailoring training scenarios to the individual player. The research is centered around three research innovations: (1) techniques for the automated modelling of players’ affective states, based on exhibited social signals, (2) techniques for the automated generation of in-game narratives tailored to the learning needs of the player, and (3) validated studies on the relation of the player behavior and game properties to learning performance. This paper describes the integration of the main results into a joint prototype

Greener pulmonary care is possible

Bij het gebruik van dosisaerosolinhalatoren door COPD- en astmapatiënten komen drijf­gassen vrij die bijdragen aan de opwarming van de aarde. Wanneer we dit type inhalatoren bij 70% van de 1,4 miljoen gebruikers veilig vervangen door klimaatvriendelijkere poeder­inhalatoren, kan de uitstoot van broeikasgassen met ongeveer 63 miljoen kg CO2-eq per jaar afnemen. Een behoorlijke milieuwinst. De goedkoopste vervangers leveren per jaar bovendien een flinke kostenbesparing op. Wij denken dat de milieu-impact in de longzorg aanzienlijk naar beneden kan

Greener pulmonary care is possible

Bij het gebruik van dosisaerosolinhalatoren door COPD- en astmapatiënten komen drijf­gassen vrij die bijdragen aan de opwarming van de aarde. Wanneer we dit type inhalatoren bij 70% van de 1,4 miljoen gebruikers veilig vervangen door klimaatvriendelijkere poeder­inhalatoren, kan de uitstoot van broeikasgassen met ongeveer 63 miljoen kg CO2-eq per jaar afnemen. Een behoorlijke milieuwinst. De goedkoopste vervangers leveren per jaar bovendien een flinke kostenbesparing op. Wij denken dat de milieu-impact in de longzorg aanzienlijk naar beneden kan

Greener pulmonary care is possible

Bij het gebruik van dosisaerosolinhalatoren door COPD- en astmapatiënten komen drijf­gassen vrij die bijdragen aan de opwarming van de aarde. Wanneer we dit type inhalatoren bij 70% van de 1,4 miljoen gebruikers veilig vervangen door klimaatvriendelijkere poeder­inhalatoren, kan de uitstoot van broeikasgassen met ongeveer 63 miljoen kg CO2-eq per jaar afnemen. Een behoorlijke milieuwinst. De goedkoopste vervangers leveren per jaar bovendien een flinke kostenbesparing op. Wij denken dat de milieu-impact in de longzorg aanzienlijk naar beneden kan

Greener pulmonary care is possible

Bij het gebruik van dosisaerosolinhalatoren door COPD- en astmapatiënten komen drijf­gassen vrij die bijdragen aan de opwarming van de aarde. Wanneer we dit type inhalatoren bij 70% van de 1,4 miljoen gebruikers veilig vervangen door klimaatvriendelijkere poeder­inhalatoren, kan de uitstoot van broeikasgassen met ongeveer 63 miljoen kg CO2-eq per jaar afnemen. Een behoorlijke milieuwinst. De goedkoopste vervangers leveren per jaar bovendien een flinke kostenbesparing op. Wij denken dat de milieu-impact in de longzorg aanzienlijk naar beneden kan.Bij het gebruik van dosisaerosolinhalatoren door COPD- en astmapatiënten komen drijf­gassen vrij die bijdragen aan de opwarming van de aarde. Wanneer we dit type inhalatoren bij 70% van de 1,4 miljoen gebruikers veilig vervangen door klimaatvriendelijkere poeder­inhalatoren, kan de uitstoot van broeikasgassen met ongeveer 63 miljoen kg CO2-eq per jaar afnemen. Een behoorlijke milieuwinst. De goedkoopste vervangers leveren per jaar bovendien een flinke kostenbesparing op. Wij denken dat de milieu-impact in de longzorg aanzienlijk naar beneden kan

Longitudinal characteristics of T2-FLAIR mismatch in IDH-mutant astrocytomas: Relation to grade, histopathology, and overall survival in the GLASS-NL cohort.

BACKGROUND: The T2-FLAIR mismatch sign is defined by signal loss of the T2-weighted hyperintense area with Fluid-Attenuated Inversion Recovery (FLAIR) on magnetic resonance imaging, causing a hypointense region on FLAIR. It is a highly specific diagnostic marker for IDH-mutant astrocytoma and is postulated to be caused by intercellular microcystic change in the tumor tissue. However, not all IDH-mutant astrocytomas show this mismatch sign and some show the phenomenon in only part of the lesion. The aim of the study is to determine whether the T2-FLAIR mismatch phenomenon has any prognostic value beyond initial noninvasive molecular diagnosis. METHODS: Patients initially diagnosed with histologically lower-grade (2 or 3) IDH-mutant astrocytoma and with at least 2 surgical resections were included in the GLASS-NL cohort. T2-FLAIR mismatch was determined, and the growth pattern of the recurrent tumor immediately before the second resection was annotated as invasive or expansive. The relation between the T2-FLAIR mismatch sign and tumor grade, microcystic change, overall survival (OS), and other clinical parameters was investigated both at first and second resection. RESULTS: The T2-FLAIR mismatch sign was significantly related to Grade 2 (80% vs 51%), longer post-resection median OS (8.3 vs 5.2 years), expansive growth, and lower age at second resection. At first resection, no relation was found between the mismatch sign and OS. Microcystic change was associated with areas of T2-FLAIR mismatch. CONCLUSIONS: T2-FLAIR mismatch in IDH-mutant astrocytomas is correlated with microcystic change in the tumor tissue, favorable prognosis, and Grade 2 tumors at the time of second resection

Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma:an open-label phase 2 trial

Background: The outcome of non-transplant eligible newly diagnosed multiple myeloma (NDMM) patients is heterogeneous, partly depending on frailty level. The aim of this study was to prospectively investigate the efficacy and safety of Ixazomib-Daratumumab-low-dose dexamethasone (Ixa-Dara-dex) in NDMM intermediate-fit patients. Methods: In this phase II multicenter HOVON-143 study, IMWG Frailty index based intermediate-fit patients, were treated with 9 induction cycles of Ixa-Dara-dex, followed by maintenance with ID for a maximum of 2 years. The primary endpoint was overall response rate on induction treatment. Patients were included from October 2017 until May 2019. Trial Registration Number: NTR6297. Findings: Sixty-five patients were included. Induction therapy resulted in an overall response rate of 71%. Early mortality was 1.5%. At a median follow-up of 41.0 months, median progression-free survival (PFS) was 18.2 months and 3-year overall survival 83%. Discontinuation of therapy occurred in 77% of patients, 49% due to progression, 9% due to toxicity, 8% due to incompliance, 3% due to sudden death and 8% due to other reasons. Dose modifications of ixazomib were required frequently (37% and 53% of patients during induction and maintenance, respectively), mainly due to, often low grade, polyneuropathy. During maintenance 23% of patients received daratumumab alone. Global quality of life (QoL) improved significantly and was clinically relevant, which persisted during maintenance treatment. Interpretation: Ixazomib-Daratumumab-low-dose dexamethasone as first line treatment in intermediate-fit NDMM patients is safe and improves global QoL. However, efficacy was limited, partly explained by ixazomib-induced toxicity, hampering long term tolerability of this 3-drug regimen. This highlights the need for more efficacious and tolerable regimens improving the outcome in vulnerable intermediate-fit patients. Funding: Janssen Pharmaceuticals, Takeda Pharmaceutical Company Limited.</p